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European Radiology Jul 2020To assess the effect of salvage hepatic vein embolization (HVE) on the volume of the future liver remnant (FLR) for patients with metastatic colorectal cancer (mCRC) and...
OBJECTIVES
To assess the effect of salvage hepatic vein embolization (HVE) on the volume of the future liver remnant (FLR) for patients with metastatic colorectal cancer (mCRC) and inadequate hypertrophy following initial portal vein embolization (PVE).
METHODS
From April 2011 to October 2018, 9 patients with mCRC underwent HVE following PVE. The right or middle hepatic vein was embolized with coils and/or vascular plugs. Liver volumes were calculated at baseline, following PVE, and following HVE, in order to assess the hypertrophic effect of PVE and HVE on the FLR.
RESULTS
Nine patients underwent HVE (n = 3, right HVE; n = 6, middle HVE) because of inadequate FLR hypertrophy following PVE. The standardized FLR increased from 0.16 (median, range 0.08-0.24) at baseline to 0.22 (median, range 0.13-0.29) following PVE (p = 0.0005) to 0.26 (median, range 0.19-0.37) following HVE (p = 0.0050). HVE was performed 40 days (median, range 19-128 days) following PVE, and assessment of FLR hypertrophy was performed 41 days (median, range 19-92 days) following HVE. Four of nine patients underwent hepatectomy; 5 patients failed to undergo hepatectomy (n = 3, inadequate hypertrophy; n = 1, disease progression; n = 1, portal hypertension). One patient required repeat HVE due to a patent accessory vein.
CONCLUSIONS
Salvage HVE is an effective technique to induce additional FLR hypertrophy in patients with mCRC and inadequate FLR after initial PVE.
KEY POINTS
• Hepatic vein embolization is effective to induce additional liver hypertrophy in surgical patients with metastatic colorectal carcinoma and inadequate hypertrophy after portal vein embolization. • Increases in future liver remnant volume are feasible in patients who receive hepatotoxic neoadjuvant systemic therapy for metastatic colorectal carcinoma. • Sequential portal vein embolization and hepatic vein embolization can be a viable technique to induce liver hypertrophy in patients with small baseline future liver remnant volumes (< 20%).
Topics: Adult; Aged; Colorectal Neoplasms; Contrast Media; Embolization, Therapeutic; Female; Hepatectomy; Hepatic Veins; Humans; Hypertrophy; Liver; Liver Neoplasms; Male; Middle Aged; Multidetector Computed Tomography; Portal Vein; Radiographic Image Enhancement; Retreatment; Retrospective Studies; Treatment Outcome
PubMed: 32144462
DOI: 10.1007/s00330-020-06746-4 -
Radiology. Artificial Intelligence Sep 2019Some patients with hepatocellular carcinoma (HCC) are more likely to experience disease progression despite transcatheter arterial chemoembolization (TACE) treatment,...
PURPOSE
Some patients with hepatocellular carcinoma (HCC) are more likely to experience disease progression despite transcatheter arterial chemoembolization (TACE) treatment, and thus would benefit from early switching to other therapeutic regimens. We sought to evaluate a fully automated machine learning algorithm that uses pre-therapeutic quantitative computed tomography (CT) image features and clinical factors to predict HCC response to TACE.
MATERIALS AND METHODS
Outcome information from 105 patients receiving first-line treatment with TACE was evaluated retrospectively. The primary clinical endpoint was time to progression (TTP) based on follow-up CT radiological criteria (mRECIST). A 14-week cutoff was used to classify patients as TACE-susceptible (TTP ≥14 weeks) or TACE-refractory (TTP <14 weeks). Response to TACE was predicted using a random forest classifier with the Barcelona Clinic Liver Cancer (BCLC) stage and quantitative image features as input as well as the BCLC stage alone as a control.
RESULTS
The model's response prediction accuracy rate was 74.2% (95% CI=64%-82%) using a combination of the BCLC stage plus quantitative image features versus 62.9% (95% CI= 52%-72%) using the BCLC stage alone. Shape image features of the tumor and background liver were the dominant features correlated to the TTP as selected by the Boruta method and were used to predict the outcome.
CONCLUSION
This preliminary study demonstrates that quantitative image features obtained prior to therapy can improve the accuracy of predicting response of HCC to TACE. This approach is likely to provide useful information for aiding HCC patient selection for TACE.
PubMed: 31858078
DOI: 10.1148/ryai.2019180021 -
Cardiovascular and Interventional... Feb 2020Peptide receptor radionuclide therapy (PRRT) and radioembolization are increasingly used in neuroendocrine neoplasms patients. However, concerns have been raised on...
PURPOSE
Peptide receptor radionuclide therapy (PRRT) and radioembolization are increasingly used in neuroendocrine neoplasms patients. However, concerns have been raised on cumulative hepatotoxicity. The aim of this sub-analysis was to investigate hepatotoxicity of yttrium-90 resin microspheres radioembolization in patients who were previously treated with PRRT.
METHODS
Patients treated with radioembolization after systemic radionuclide treatment were retrospectively analysed. Imaging response according to response evaluation criteria in solid tumours (RECIST) v1.1 and clinical response after 3 months were collected. Clinical, biochemical and haematological toxicities according to common terminology criteria for adverse events (CTCAE) v4.03 were also collected. Specifics on prior PRRT, subsequent radioembolization treatments, treatments after radioembolization and overall survival (OS) were collected.
RESULTS
Forty-four patients were included, who underwent a total of 58 radioembolization procedures, of which 55% whole liver treatments, at a median of 353 days after prior PRRT. According to RECIST 1.1, an objective response rate of 16% and disease control rate of 91% were found after 3 months. Clinical response was seen in 65% (15/23) of symptomatic patients after 3 months. Within 3 months, clinical toxicities occurred in 26%. Biochemical and haematological toxicities CTCAE grade 3-4 occurred in ≤ 10%, apart from lymphocytopenia (42%). Radioembolization-related complications occurred in 5% and fatal radioembolization-induced liver disease in 2% (one patient). A median OS of 3.5 years [95% confidence interval 1.8-5.1 years] after radioembolization for the entire study population was found.
CONCLUSION
Radioembolization after systemic radionuclide treatments is safe, and the occurrence of radioembolization-induced liver disease is rare.
LEVEL OF EVIDENCE
4, case series.
Topics: Adult; Aged; Aged, 80 and over; Brachytherapy; Female; Humans; Liver Neoplasms; Male; Microspheres; Middle Aged; Neuroendocrine Tumors; Receptors, Peptide; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; Treatment Outcome; Yttrium Radioisotopes
PubMed: 31646375
DOI: 10.1007/s00270-019-02350-2 -
Cardiovascular and Interventional... Mar 2019Radioembolization of liver metastases of neuroendocrine neoplasms (NEN) has shown promising results; however, the current literature is of limited quality. A large...
PURPOSE
Radioembolization of liver metastases of neuroendocrine neoplasms (NEN) has shown promising results; however, the current literature is of limited quality. A large international, multicentre retrospective study was designed to address several shortcomings of the current literature.
MATERIALS
244 NEN patients with different NEN grades were included.
METHODS
Primary outcome parameters were radiologic response 3 and 6 months after treatment according to RECIST 1.1 and mRECIST. Secondary outcome parameters included clinical response, clinical and biochemical toxicities.
RESULTS
Radioembolization resulted in CR in 2%, PR in 14%, SD in 75% and PD 9% according to RECIST 1.1 and in CR in 8%, PR in 35%, SD in 48% and PD in 9% according to mRECIST. Objective response rates improved over time in 20% and 26% according to RECIST 1.1. and mRECIST, respectively. Most common new grade 3-4 biochemical toxicity was lymphocytopenia (6.7%). No unexpected clinical toxicities occurred. Radioembolization-specific complications occurred in < 4%. In symptomatic patients, improvement and resolution of symptoms occurred in 44% and 34%, respectively. Median overall survival from first radioembolization was 3.7, 2.7 and 0.7 years for G1, G2 and G3, respectively. Objective response is independent of NEN grade or primary tumour origin. Significant prognostic factors for survival were NEN grade/Ki67 index, ≥ 75% intrahepatic tumour load, the presence of extrahepatic disease and disease control rate according to RECIST 1.1.
CONCLUSION
Safety and efficacy of radioembolization in NEN patients was confirmed with a high disease control rate of 91% in progressive patients and alleviation of NEN-related symptoms in 79% of symptomatic patients.
LEVEL OF EVIDENCE
4.
Topics: Brachytherapy; Follow-Up Studies; Humans; Liver Neoplasms; Microspheres; Neuroendocrine Tumors; Retrospective Studies; Survival Analysis; Treatment Outcome; Yttrium Radioisotopes
PubMed: 30603975
DOI: 10.1007/s00270-018-2148-0 -
Molecular Genetics and Metabolism... Dec 2018Glucagon receptor (GCGR) defect (Mahvash disease) is an autosomal recessive hereditary pancreatic neuroendocrine tumor (PNET) syndrome that has only been reported in...
Glucagon receptor (GCGR) defect (Mahvash disease) is an autosomal recessive hereditary pancreatic neuroendocrine tumor (PNET) syndrome that has only been reported in adults with pancreatic α cell hyperplasia and PNETs. We describe a 7-year-old girl with persistent hyperaminoacidemia, notable for elevations of glutamine (normal ammonia), alanine (normal lactate), dibasic amino acids (arginine, lysine and ornithine), threonine and serine. She initially was brought to medical attention by an elevated arginine on newborn screening (NBS) and treated for presumed arginase deficiency with a low protein diet, essential amino acids formula and an ammonia scavenger drug. This treatment normalized plasma amino acids. She had intermittent emesis and anorexia, but was intellectually normal. Arginase enzyme assay and sequencing and deletion/duplication analysis were normal. Treatments were stopped, but similar pattern of hyperaminoacidemia recurred. She also had hypercholesterolemia type IIa, with only elevated LDL cholesterol, despite an extremely lean body habitus. Exome sequencing was initially non-diagnostic. Through a literature search, we recognized the pattern of hyperaminoacidemia was strikingly similar to that reported in the knockout mice. Subsequently the patient was found to have an extremely elevated plasma glucagon and a novel, homozygous c.958_960del (p.Phe320del) variant in . Functional studies confirmed the pathogenicity of this variant. This case expands the clinical phenotype of GCGR defect in children and emphasizes the clinical utility of plasma amino acids in screening, diagnosis and monitoring glucagon signaling interruption. Early identification of a GCGR defect may provide an opportunity for potential beneficial treatment for an adult onset tumor predisposition disease.
PubMed: 30294546
DOI: 10.1016/j.ymgmr.2018.09.006 -
European Journal of Cancer (Oxford,... Oct 2018Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer with approximately half a million cases diagnosed each year worldwide. HNSCC has a poor...
BACKGROUND
Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer with approximately half a million cases diagnosed each year worldwide. HNSCC has a poor survival rate which has not improved for over 30 years. The molecular pathogenesis of HNSCCs remains largely unresolved; there is high prevalence of p53 mutations and EGFR overexpression; however, the contribution of these molecular changes to disease development and/or progression remains unknown. We have recently identified microRNA miR-196a to be highly overexpressed in HNSCC with poor prognosis. Oncogenic miR-196a directly targets Annexin A1 (ANXA1). Although increased ANXA1 expression levels have been associated with breast cancer development, its role in HNSCC is debatable and its functional contribution to HNSCC development remains unclear.
METHODS
ANXA1 mRNA and protein expression levels were determined by RNA Seq analysis and immunohistochemistry, respectively. Gain- and loss-of-function studies were performed to analyse the effects of ANXA1 modulation on cell proliferation, mechanism of activation of EGFR signalling as well as on exosome production and exosomal phospho-EGFR.
RESULTS
ANXA1 was found to be downregulated in head and neck cancer tissues, both at mRNA and protein level. Its anti-proliferative effects were mediated through the intracellular form of the protein. Importantly, ANXA1 downregulation resulted in increased phosphorylation and activity of EGFR and its downstream PI3K-AKT signalling. Additionally, ANXA1 modulation affected exosome production and influenced the release of exosomal phospho-EGFR.
CONCLUSIONS
ANXA1 acts as a tumour suppressor in HNSCC. It is involved in the regulation of EGFR activity and exosomal phospho-EGFR release and could be an important prognostic biomarker.
Topics: Annexin A1; Cell Proliferation; ErbB Receptors; Exosomes; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Mutation; Phosphatidylinositol 3-Kinase; Phosphorylation; Proto-Oncogene Proteins c-akt; Signal Transduction; Squamous Cell Carcinoma of Head and Neck; Tumor Suppressor Proteins
PubMed: 30142511
DOI: 10.1016/j.ejca.2018.07.123 -
The Journal of Clinical Endocrinology... Sep 2018Hyperglucagonemia in the absence of glucagonomas is rare. Biallelic-inactivating mutations in the glucagon receptor gene (GCGR) cause glucagon cell hyperplasia and...
CONTEXT
Hyperglucagonemia in the absence of glucagonomas is rare. Biallelic-inactivating mutations in the glucagon receptor gene (GCGR) cause glucagon cell hyperplasia and neoplasia (GCHN), also termed Mahvash syndrome. Here, we report the first case to our knowledge of GCHN presenting with hypercalcemia and demonstrate a unique relationship between calcium and α-cell hyperplasia.
CASE DESCRIPTION
A 47-year-old man presented with severe PTH-independent hypercalcemia, 13.95 mg/dL (3.48 mmol/L). Imaging and extensive pathology tests yielded no conclusive cause. Glucagon levels >300 times the upper limit of normal were discovered. Subtotal pancreatectomy identified α-cell hyperplasia and neoplasia with metastatic disease in lymph nodes. Genomic analysis confirmed a homozygous missense variant in GCGR (Asp63Asn). This is a previously described pathologic variant and has a known association with GCHN.
CONCLUSIONS
Inactivating mutations of the glucagon receptor gene lead to nonfunctional hyperglucagonemia and are associated with GCHN. Homozygous or compound heterozygous GCGR mutations are associated with α-cell hyperplasia, a known precursor to pancreatic neuroendocrine tumors that can metastasize. Hypercalcemia is an unreported consequence of GCHN with an unclear mechanism.
Topics: Carcinoma, Neuroendocrine; Glucagon; Glucagon-Secreting Cells; Humans; Hypercalcemia; Hyperplasia; Lymphatic Metastasis; Male; Middle Aged; Mutation, Missense; Pancreatic Neoplasms; Paraneoplastic Syndromes; Receptors, Glucagon; Syndrome
PubMed: 30032256
DOI: 10.1210/jc.2018-01074 -
Pancreas 2018
Review
Topics: Animals; Disease Models, Animal; Genetic Predisposition to Disease; Humans; Mice; Mutation; Neoplastic Syndromes, Hereditary; Neuroendocrine Tumors; Pancreatic Neoplasms; Receptors, Glucagon
PubMed: 29702528
DOI: 10.1097/MPA.0000000000001044 -
Journal of Vascular Surgery. Venous and... Sep 2017Our primary purpose was to assess the impact of an inferior vena cava filter retrieval algorithm in a cancer population. Because cancer patients are at persistently...
OBJECTIVE
Our primary purpose was to assess the impact of an inferior vena cava filter retrieval algorithm in a cancer population. Because cancer patients are at persistently elevated risk for development of venous thromboembolism (VTE), our secondary purpose was to assess the incidence of recurrent VTE in patients who underwent filter retrieval.
METHODS
Patients with malignant disease who had retrievable filters placed at a tertiary care cancer hospital from August 2010 to July 2014 were retrospectively studied. A filter retrieval algorithm was established in August 2012. Patients and referring physicians were contacted in the postintervention period when review of the medical record indicated that filter retrieval was clinically appropriate. Patients were classified into preintervention (August 2010-July 2012) and postintervention (August 2012-July 2014) study cohorts. Retrieval rates and clinical pathologic records were reviewed.
RESULTS
Filter retrieval was attempted in 34 (17.4%) of 195 patients in the preintervention cohort and 66 (32.8%) of 201 patients in the postintervention cohort (P < .01). The median time to filter retrieval in the preintervention and postintervention cohorts was 60 days (range, 20-428 days) and 107 days (range, 9-600 days), respectively (P = .16). In the preintervention cohort, 49 of 195 (25.1%) patients were lost to follow-up compared with 24 of 201 (11.9%) patients in the postintervention cohort (P < .01). Survival was calculated from the date of filter placement to death, when available. The overall survival for patients whose filters were retrieved was longer compared with the overall survival for patients whose filters were not retrieved (P < .0001). Of the 80 patients who underwent successful filter retrieval, two patients (2.5%) suffered from recurrent VTE (n = 1 nonfatal pulmonary embolism; n = 1 deep venous thrombosis). Both patients were treated with anticoagulation without filter replacement.
CONCLUSIONS
Inferior vena cava filter retrieval rates can be significantly increased in patients with malignant disease with a low rate (2.5%) of recurrent VTE after filter retrieval.
Topics: Adult; Aged; Aged, 80 and over; Algorithms; Female; Follow-Up Studies; Hospitals, University; Humans; Incidence; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Retrospective Studies; Survival Rate; Treatment Outcome; United States; Vena Cava Filters; Venous Thromboembolism
PubMed: 28818223
DOI: 10.1016/j.jvsv.2017.05.017 -
Oncology 2017Hepatocellular carcinoma (HCC) prognosis depends on clinicopathological features in addition to the treatment provided. We aimed to assess the natural history of TNM...
BACKGROUND
Hepatocellular carcinoma (HCC) prognosis depends on clinicopathological features in addition to the treatment provided. We aimed to assess the natural history of TNM stage I HCC tumors which received different treatment over a period of 20 years.
METHODS
Between 1992 and 2011, a total of 397 stage I HCC patients were included. Detailed information was retrieved from MD Anderson Cancer Center patients' medical records. The Kaplan-Meier method was used to calculate patients' overall survival (OS). Cox regression analysis was used to calculate the estimated hazard ratio and 95% confidence interval of different prognostic factors.
RESULTS
Out of 397 patients, 67.5% were males, 42.8% had hepatitis-related HCC, and 59.7% had underlying cirrhosis. After adjustment for confounding factors, we found that all therapeutic modalities were associated with a significant mortality rate reduction with an OS of 63, 42.03, 34.3, and 22.1 months among patients treated with surgery, ablation, local, and systemic therapy, respectively. A restricted analysis of cirrhotic and noncirrhotic patients showed that ablative and local therapy were significantly associated with a longer OS compared to systemic therapy.
CONCLUSION
TNM stage I HCC patients have a favorable prognosis regardless of the type of treatment. Notably, ablative and local therapy significantly improved OS compared to systemic therapy.
Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Catheter Ablation; Chemoembolization, Therapeutic; Disease-Free Survival; Female; Hepatectomy; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Niacinamide; Phenylurea Compounds; Prognosis; Retrospective Studies; Sorafenib; Treatment Outcome; United States
PubMed: 28683459
DOI: 10.1159/000455957